Vitamin D binding protein genotype frequency in familial Mediterranean fever patients.

Objective: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent short episodes (1-3 days) of inflammation and fever. FMF is associated with MEFV gene mutations but some patients with FMF symptoms do not have a mutation in the coding region of the MEFV gene. Vitamin D binding protein (VDBP) has important functions, including transporting vitamin D and its metabolites to target cells. Circulating levels of vitamin D are decreased in several inflammatory conditions, including FMF. Thus, we hypothesize that VDBP may play a crucial role in FMF pathogenesis, in addition to the MEFV gene. Method: VDBP genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism in 107 FMF patients and 25 healthy individuals without FMF or family history. For this, after amplification of genomic DNA, PCR products were digested with restriction enzymes HaeIII and StyI and evaluated electrophoretically. Results: We observed a statistically significant difference in the frequency of the 1F-2 genotype. The frequency of allele 2 was significantly higher and allele 1S was significantly lower compared to the [MEFV(-)] group and healthy controls (p = 0.034, 0.001, and 0.012, respectively). We observed a significant association between the presence of allele 2 and amyloidosis (p = 0.026) and arthritis (p = 0.044) in the [MEFV(-)] group. Conclusion: Our results suggest that FMF symptoms in the absence of MEFV gene mutations may be due to the presence of VDBP allele 2. Therefore, VDBP genotype may explain the symptoms in FMF [MEFV(-)] patients.

Hepatitis A virus vaccination in childhood-onset systemic lupus erythematosus.

OBJECTIVES: Vaccination of systemic lupus erythematosus patients with non-live vaccines may decrease vaccine-preventable infections and mortalities. In the present study, we aimed to compare the immunogenicity and safety of inactivated hepatitis A vaccination in childhood-onset systemic lupus erythematosus and healthy subjects. METHODS: A total of 30 childhood-onset systemic lupus erythematosus and 39 healthy participants who were seronegative for hepatitis A received two doses of the hepatitis A vaccine in a 0- and 6-month schedule. Hepatitis A virus (HAV) IgG antibodies were measured before vaccination and 7 months after the vaccination. RESULTS: Although anti-HAV IgG antibody titers after vaccination were found to be somewhat lower in children with systemic lupus erythematosus than that of the healthy subjects ( p < 0.05), the difference in seroconversion rate was insignificant between childhood-onset systemic lupus erythematosus patients ( n = 24/30, 80%) and healthy controls ( n = 33/39, 84.6%). There was no increase in median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores and anti-ds DNA levels after the vaccination procedure. Seroconversion rates in childhood-onset systemic lupus erythematosus patients were not affected by medication, high disease activity (SLEDAI-2K >6) and anti-ds DNA positivity. None of the patients experienced any flare or adverse reaction throughout the study. CONCLUSIONS: According to these results, we conclude that inactivated hepatitis A vaccine is safe and well tolerated in childhood-onset systemic lupus erythematosus patients, with no adverse events or increase in activity. Immunogenicity to the hepatitis A vaccine was adequate, with a seropositivity rate of 80%.

Juvenile systemic lupus erythematosus in Turkey: demographic, clinical and laboratory features with disease activity and outcome.

Objectives This paper aims to assess in a retrospective fashion the clinical and laboratory features, severity and outcome of juvenile systemic lupus erythematosus (jSLE) from a referral center in Turkey. Methods We have included all jSLE patients ( n = 92) diagnosed according to the revised American College of Rheumatology 1997 criteria between January 2004 and January 2017. Results The most prevalent clinical feature in our cohort was mucocutaneous manifestations (97.8%), followed by constitutional (81.5%), hematological (59.8%) and musculoskeletal manifestations (56.5%). Renal involvement was observed in 38% ( n = 35) of the patients, whereas biopsy-proven lupus nephritis was detected in 29.3% ( n = 27) of the cohort. Neurologic involvement was seen in 15 (16.3%) individuals. Among the patients positive for anticardiolipin IgM and/or IgG ( n = 11, 12%), only three developed antiphospholipid antibody syndrome. The mean SLEDAI-2K scores at disease onset (10.5 ± 4.8) showed a substantial decrease at last visit (4.3 ± 4.6). One-quarter of the patients (26.1%, n = 24) had damage according to the PedSDI criteria with a mean score of 0.45 ± 1.0 (range 0-7). When the PedSDI damage items were evaluated individually, growth failure was the most frequent damage criterion ( n = 6), followed by seizure ( n = 5). Two patients died during the designated study period of end-stage renal disease. The five-year and 10-year survival rate of our cohort was 100% and 94.4%, respectively. Conclusions Given the lower frequency of nephritis and central nervous system disease and lower basal disease activity and damage scores, we could conclude that children with jSLE in Turkey have a more favorable course compared to Asian and African American children, as expected from Caucasian ethnicity.

Pentraxin-3 levels are associated with vasculitis and disease activity in childhood-onset systemic lupus erythematosus.

Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune disease characterized by inflammatory organ damage by means of vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory processes, predominantly from endothelial cells. In adult studies, PTX3 has shown to be an indicator of active vasculitis both in large-vessel and small-vessel vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated with disease activity, and with some of the clinical manifestations and laboratory parameters. We aimed to ascertain if PTX3 might be a significant mediator in cSLE and if it might indicate active vasculitis during the course of the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and 41 healthy subjects. We have investigated its relation with disease activity, damage, clinical features, laboratory parameters and medications. Results Serum levels of PTX3 were found to be increased in cSLE compared to healthy controls (mean ± SD; 10.6 ± 8.2 ng/mL vs 2.7 ± 1.3 ng/mL, p < 0.001). PTX3 concentrations were also in correlation with SLEDAI-2K ( r = 0.57, p < 0.001). When viewed from the clinical perspective, serum PTX3 levels were significantly higher only in patients with active vasculitis ( p < 0.001), Raynaud phenomenon ( p = 0.006) and mucocutaneous manifestations ( p < 0.001). However, an association between PTX3 and age, age at disease onset, disease duration, complement levels, PedSDI score (pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected. Conclusions Patients with cSLE have increased levels of serum PTX3 compared to healthy controls. Thus, serum PTX-3 level might be a significant mediator in cSLE. Apart from these, the results support that PTX3 reflects active cutaneous vasculitis in cSLE and correlates with disease activity.

Cross-cultural adaptation, reliability, and validity of the Turkish version of PedsQL 3.0 Arthritis Module: a quality-of-life measure for patients with juvenile idiopathic arthritis in Turkey.

PURPOSE: The aim of this study was to describe the cultural adaptation, validity, and reliability of a Turkish version of the pediatric quality-of-life inventory (PedsQL) 3.0 Arthritis Module in a population with juvenile idiopathic arthritis (JIA). METHODS: A total of 169 patients with JIA and their parents were enrolled in the study. The Turkish version of the childhood health assessment questionnaire (CHAQ) was used to evaluate the validity of related domains in the PedsQL 3.0 Arthritis Module. Both the PedsQL 3.0 Arthritis Module and CHAQ were filled out by children over 8 years of age and by the parents of children 2-7 years of age. RESULTS: Internal reliability was poor to excellent (Cronbach's alpha coefficients 0.56-0.84 for self-reporting and 0.63-0.82 for parent reporting), and interobserver reliability varied from good to excellent (intraclass correlation coefficient (ICC) 0.79-0.91 for self-reporting and 0.80-0.88 for parent reporting) for the total scores of the PedsQL 3.0 Arthritis Module. Parent-child concordance for all scores was moderate to excellent (ICC 0.42-0.92). The PedsQL 3.0 Arthritis Module and CHAQ were highly positively correlated, with coefficients from 0.21 to 0.76, indicating concurrent validity. CONCLUSIONS: We demonstrated the reliability and validity of quality-of-life measurement using the Turkish version of the PedsQL 3.0 Arthritis Module in our sociocultural context. The PedsQL 3.0 Arthritis Module can be utilized as a tool for the evaluation of quality of life in patients with JIA aged 2-18 years.

Juvenile and adult-onset scleroderma: Different clinical phenotypes.

OBJECTIVES: Systemic sclerosis (SSc) represents extremely rare disease with majority of data coming from adults. Studies comparing juvenile- (jSSc) and adult-onset (aSSc) patients are limited. We aimed to compare clinical features, treatment modalities and survival rates of jSSc and aSSc patients. METHODS: A retrospective study among pediatric and adult Scl patients has been performed. Demographic characteristics, clinical features, autoantibody profiles, and treatment data were retrieved from the databases. Survival analysis was done using Kaplan-Meier plot and factors associated with mortality were identified with multiple regression analysis. RESULTS: A total of 158 adults and 58 juvenile Scl patients were identified. The mean age at the disease onset was 37±14.7 vs. 8.8 ± 4.1 years, mean age at diagnosis 42±15.2 vs. 10.4 ± 3.8 years and mean follow-up duration was 6.3 ± 4.9 years vs. 6.6 ± 4.9 years for aSSc and jSSc patients, respectively. The frequency of interstitial lung disease (ILD) (50.9% vs 30%, p<0.001) and systemic hypertension (17.9% vs 0, p = 0.009) was significantly higher among aSSc. While aSSc patients had presented mostly with limited cutaneous subset (74.1%), diffuse cutaneous subset was the dominant subset among jSSc (76.7%), (p<0.001). The mortality rate was significantly higher among adults (p = 0.005). The ILD (p = 0.03) and cardiac insufficiency (p = 0.05) were independent risk factors of mortality in both aSSc and jSSc patients. CONCLUSION: Juvenile and adult-onset Scl represent rarely seen conditions with different clinical phenotypes. Pediatric patients with LS are more commonly seen by pediatric rheumatologists, in contrary to adults. Diffuse disease subset is the dominant form among juvenile patients, whereas limited form is the main disease subset among adults. On the other hand, juvenile-onset patients have a better survival than those with adult-onset.

Increased expression of exon 2 deleted MEFV transcript in familial Mediterranean fever patients.

A defect in MEFV gene expression regulation has been implicated in familial Mediterranean fever (FMF) etiopathophysiology. Here we show significantly higher expression level in second exon lacking MEFV transcript in FMF patients compared with healthy controls (P=0.026). Our results also point out a possible role of exon 2 deleted MEFV transcript in FMF pathogenesis.

Factors affecting survival in juvenile systemic sclerosis.

OBJECTIVES: To determine whether demographic, clinical and immunological features may predict the outcome in juvenile SSc (JSSc). METHODS: Clinical and laboratory characteristics of patients with JSSc collected from paediatric rheumatology centres worldwide were analysed. First, univariate tests identified those features significantly related with fatal outcome, and then multivariate logistic regression analysis was applied to determine the predictors of mortality. RESULTS: One hundred and thirty-four patients from 40 centres were eligible for the analysis. Sixteen patients died and a rapidly fatal course was observed in most of them: 4/16 died within 1 yr after diagnosis and 10/16 within 5 yrs. At the moment of diagnosis, patients with poor outcome showed a significantly higher frequency of internal organ involvement, particularly cardiac, respiratory and gastrointestinal systems. No significant difference emerged for entity of skin, vascular and musculo-skeletal involvement, nor for auto-antibodies profile and laboratory tests. Multivariate analysis showed the following factors to be significant predictors of mortality: fibrosis on chest X-rays [odds ratio (OR) 11.2], raised creatinine levels (OR 22.7) and pericarditis (OR 41.3), while a short disease duration at diagnosis conferred protection (OR 0.3). CONCLUSIONS: All patients with JSSc and fatal outcome were affected by the diffuse form of the disease, and most of them showed a very rapid progression and early signs of internal organ involvement. This suggests that, in children, SSc may have two possible courses: a rapid development of internal organ failure leading to severe disability and eventually to death, or a slow course of the disease with lower mortality.

MEFV gene 3'-UTR Alu repeat polymorphisms in patients with familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF), an autosomal recessively inherited autoinflammatory disorder, is caused by missense mutations in the pyrin-encoding MEFV gene. The MEFV mutations can be detected in the majority of FMF patients, but there is an important proportion of patients with the FMF phenotype who carry a single or no coding region mutation. This study aimed to investigate the promoter region and 3'-UTR polymorphisms of the MEFV gene in a group of FMF patients with no coding region mutations, to identify variations with a possible role in the regulation of MEFV expression. METHODS: The study group consisted of 289 patients with FMF and 103 ethnically-matched healthy individuals of Turkish origin. All individuals were first genotyped for the five most commonly observed mutations (M694V, M680I, V726A, E148Q and M694I). Then, the coding regions of the MEFV gene in patients carrying none of the 5 mutations were amplified and screened using single-stranded conformation polymorphism and DNA sequencing. After the exclusion of patients with mutations in exons, the promoter and 3'-UTR regions of the MEFV gene were investigated in the remainder. For the haplotype analysis, all study groups were genotyped for two of the 3'-UTR single nucleotide polymorphisms (SNP). RESULTS: Genotyping for five mutations revealed 186 patients (64.4%) with two mutations, 61 patients (21.1%) with one mutation, and 42 patients (14.5%) with no mutation. The carrier rate for healthy controls was found to be 10%. After screening all 10 exons in the patients with none of the 5 mutations, we identified 36 patients (12.5%) who had no coding region mutations. Analysis of the 3'-UTR region in these patients showed two Alu repeats (AluSx and AluSq), which were located in the 3'-UTR of the reference mRNA sequence. Sequencing of the 3'-UTR of the MEFV gene showed several SNPs that were clustered in 2 haplotypes. When we genotyped all study groups for two of the 3'-UTR SNPs (rs2741918 and rs450021), we observed a significant increase in the frequency of heterozygotes for the 3'-UTR haplotypes in the FMF patients with no coding region polymorphisms compared to the healthy controls (75% versus 48.5%, p=0.006, OR=3.2, 95% CI 1.4-7.4). CONCLUSION: This study showed a group of 3'-UTR polymorphisms in the MEFV gene that are clustered in two haplotypes. In addition, a genetic association was observed between 3'-UTR polymorphisms and the FMF patients with no coding region mutations. These findings may suggest a role for 3'-UTR sequences in the regulation of MEFV expression.

Dissection of the abdominal aorta in a child with Takayasu's arteritis.

Takayasu's arteritis is a chronic inflammatory disease that primarily involves the aorta and its main branches. Varying degrees of narrowing, occlusion, or dilatation develop in the involved vessel segments. However, dissection of the aorta is quite rare in this disease, and it may develop particularly after angioplasty. We report a very rare case of Takayasu's arteritis with dissection of the abdominal aorta just distal to the origin of the inferior mesenteric artery in a 9-year-old girl. She was treated conservatively with close follow-up. At the end of 1 year's follow-up, the dissection of the aorta did not show progression, and new lesions were not identified. To our knowledge, this patient is the youngest child presented with arterial dissection as the initial manifestation of the disease.

Are carriers for MEFV mutations "healthy"?

OBJECTIVE: We aimed to compare whether carriers for the MEFV mutations display an increase or decrease in certain features. We compared the frequency of a number of inflammatory symptoms and diseases in carriers and a control population. METHODS: A questionnaire was designed to be applied to parents of children with FMF and a control group of parents. Clinical features and some diseases including the frequency of febrile episodes, abdominal pain, arthralgia, prophylaxis with penicillin, acute rheumatic fever, rheumatoid arthritis, vasculitis, spondyloarthropathy, urinary tract infection, asthma, allergy, irritable bowel disease, appendectomy and tonsillectomy were inquired. 676 parents of 440 children with FMF were surveyed in this study. Controls (n: 774) were selected as parents of healthy children. RESULTS: The presence of febrile episodes more than four per year, arthralgia, past diagnosis for acute rheumatic fever, rheumatoid arthritis and prophylaxis of penicillin, acute rheumatic fever, and rheumatoid arthritis were significantly higher in asymptomatic parents for the MEFV mutations compared to controls. The frequency of allergy was found to be significantly lower in the asymptomatic parents as compared to controls. There was no significant difference at the frequency of urinary tract infection and tonsillectomy between the parents of the patents and controls. CONCLUSIONS: We suggest that one MEFV mutation may indeed be conferring a heightened inflammation as suggested by the increased frequency in inflammatory symptoms. The carrier status for MEFV mutations seem to be unique, in that they cause an alteration in the state of "health".

Juvenile chronic arthritis in a Turkish population.

The clinical characteristics of 147 Turkish patients with juvenile chronic arthritis seen between 1980 and 1988 were analyzed retrospectively. There was a male predominance (1.3:1), and a relatively low occurrence of early onset pauciarticular disease (16%), chronic anterior uveitis (7%) and positive antinuclear antigens (6%), but a high incidence of secondary amyloidosis (10%) was seen.

The Turkish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Turkish language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Turkish CHAQ CHQ were fully validated with 3 forward and 3 backward translations. A total of 145 subjects were enrolled: 85 patients with JIA (35% systemic onset, 41% polyarticular onset, and 24% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, and polyarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, and polyarticular onset having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Turkish version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Growth and IGF-1 levels of children with familial Mediterranean fever on colchicine treatment.

OBJECTIVE: To evaluate growth process and insulin like growth factor-1 (IGF-1) levels in children with familial Mediterranean fever (FMF). METHODS: This prospective study group consisted of 51 children with FMF under colchicine therapy (20 boys, 31 girls) and 42 healthy children (22 boys, 20 girls). All children were prepubertal. Bone ages and IGF-1 levels were determined in all cases. Height velocity (HV), height standard deviation score (SDS), target height and target height SDS were calculated. RESULTS: There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and diseased subjects. HV of children with FMF did not differ significantly from the control group. There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and FMF subjects. HV of children with FMF did not differ significantly from the control group. There was no significant correlation between disease duration, number of attacks, erythrocyte sedimentation rate and HV, HSDS and IGF-1 levels of FMF patients. There was positive correlation between cumulative colchicine dose and HV (r = 0.29). CONCLUSION: Growth and IGF-1 levels of children with FMF do not differ from their healthy peers. However, there was positive correlation between HV and cumulative colchicine dose. This study suggests that colchicine not only has no adverse influence on growth, but more by suppressing disease activity and inflammation it has an enhancing role.

Erythromelalgia associated with hypertension and leukocytoclastic vasculitis in a child.

Erythromelalgia is an acrocyanotic rheumatic disease presenting with erythema, and pain and a burning sensation in the hands and feet; it is rarely encountered during childhood. Hot or warm conditions may precipitate pain and erythema in the extremities and the symptoms may regress upon the application of cold water. The disease is usually secondary to other systemic diseases in adults. On the other hand, it is idiopathic in children. This article describes a case of erythromelalgia presenting with leukocytoclastic vasculitis and hypertension in a 7-year-old child who responded to therapy with prednisolone and phenoxybenzamine.

Tubular markers in children with insulin-dependent diabetes mellitus.

The aim of the present study was to investigate the prevalence of tubular dysfunction and to assess the clinical significance of low-molecular-weight proteinuria and enzymuria in children with insulin-dependent diabetes mellitus (IDDM). N.acetyl-beta-D-glucosaminidase (NAG) and beta-microglobulin (beta 2 M) excretion was determined in 52 children with insulin-dependent diabetes mellitus and 28 controls. Patients were grouped according to the duration of diabetes: group 1 (n = 7): less than one year; group 2 (n = 27): one to five years; groups 3 (n = 18): greater than five years. Both parameters were significantly increased in groups 2 and 3 compared to controls. Urinary beta 2 M levels correlated significantly with albuminuria and HbA1C, while urinary NAG levels correlated only with HbA1C. Two to four samples were obtained from 35 of 52 diabetic patients in the study group at one-month intervals. Of these, 23 patients had elevated NAG levels, and 22 patients increased beta 2 M excretion. However, only six patients displayed persistent enzymuria, and nine low-molecular-weight proteinuria. The mean (SD) of coefficients of variation of each patient was 50.45 (+/-28.24) for NAG and 68.25 (+/-42.57) for beta 2 M excretion. We concluded that early tubular dysfunction and/or damage occurs in IDDM but is not established in the majority of children.

Superior vena cava syndrome as a result of thrombosis in a child with nephrotic syndrome.

A three-year-old nephrotic girl is presented with vena cava superior syndrome. Angiography showed obliteration of the distal ends of both axillary veins and echocardiographic examination revealed a mobile mass in the right atrium. A thrombus originating from the vena cava superior with a stalk extending to the right atrium was surgically removed. To our knowledge, vena cava superior thrombosis in nephrotic syndrome has not been reported previously.

Frequency of antinuclear antibodies and rheumatoid factor in healthy Turkish children.

The frequency of antinuclear antibodies (ANA) and rheumatoid factor (RF) was investigated in 118 apparently healthy children (56 male, 62 female). The mean age was 9.8+/-2.3 years. Antinuclear antibodies (ANA) were detected by indirect immunofluorescence, using a Hep-2 cell substrate. Nephelometry was used to quantify RF in 116 children. Five serum samples (4%, 3M, 2F) were ANA-positive in low titers and all had a speckled pattern. None of the ANA-positive children had other extractable antinuclear antibodies. Rheumatoid factor (RF) was over 25 IU/ml in four children (3%, 3F, 1M). None of these was positive for both antibodies. Our results suggest a similar frequency of ANA in healthy Turkish children even with a Hep-2 cell substrate, when compared to results of other reports. On the other hand, RF was more frequent than in other reported series.

Hepatitis B virus vaccination in children with steroid sensitive nephrotic syndrome: immunogenicity and safety?

We investigated the efficacy and safety of Hepatitis B vaccine (HBVac) in steroid sensitive nephrotic syndrome (SSNS) children. 41 patients with SSNS and 30 controls were vaccinated with HBVac(Engerix B(®)). Patients were divided into 3 subgroups:full dose steroid users, alternate-day steroid users and steroid non-users. Seroconversion rate was lower in steroid users than non-users at the 6th(p=0.015) and 12th(p=0.036) months. Antibody to Hepatitis B surface antigen(HBsAb) titers were significantly different between subgroups and controls at the 15th month. However, HBsAb and response rates were not different between subgroups at the 12th and 15th months (p>0.05). Five patients were unresponsive to HBVac. Relapse rates after the vaccination were higher than those in the prevaccination period (p=0.002). HBVac is less effective in producing immune response in SSNS children with steroid therapy. HBVac may trigger relapse in some patients. We recommend HBVac to SSNS children with low dose steroid therapy or after steroids are discontinued.

Clinical characteristics of pediatric-onset neuro-Behçet disease.

OBJECTIVES: Neurologic involvement in the pediatric population with Behçet disease (BD) is limited to case reports. The aim of this study is to examine the frequency and type of neurologic involvement in pediatric patients with BD. METHODS: Medical records of 728 patients with a diagnosis of neuro-BD (NBD) of 2 large BD cohorts followed in Istanbul University were included in the study. Patients with an onset of both systemic and neurologic symptoms at or before age 16 (pediatric neuro-BD) were identified. Demographic and clinical characteristics of pediatric patients with NBD were compared with adult patients with NBD. RESULTS: There were 26 cases with pediatric BD (3.6%) and 702 (96.4%) adult-onset patients. Gender ratio was equal in the general pediatric BD cohort, whereas male/female ratio was 5.5/1 in pediatric NBD cases. Mean age at BD onset and neurologic involvement onset were 13.0 ± 3.0 and 13.5 ± 2.4, respectively, and in the adult population mean age at onset of BD was 26.7 ± 8.0 and neurologic involvement occurred a mean of 5.3 ± 4.5 years later. Clinical and MRI evaluation revealed that 3 children had CNS parenchymal involvement and 23 had dural venous sinus thrombosis (88.5%). We observed parenchymal involvement in 74.8% of the adults, contrary to the low 17.2% of cases with venous sinus thrombosis. CONCLUSIONS: Pediatric NBD comprises 3.6% of our whole NBD cohort, with a male predominance, mainly in the form of dural venous sinus thrombosis, whereas in the adult NBD population the dominant form of neurologic involvement is parenchymal, suggesting that the pathogenesis of NBD may be different according to the age at disease onset.